The chances of survival for infants with inadequate intestinal function may be improved by increasing the absorptive capacity of the existing small intestine or by providing additional mucosal surface area. Although several substances have been identified that appear to stimulate growth of small intestine mucosa, no data are available on the enhancement of intestinal function following chronic administration of these substances. Investigation of the physiologic and pharmacologic roles of gastrointestinal hormones has produced data suggesting that gastrin, and perhaps cholecystokinin and enteroglucagon, are trophic agents for small intestine mucosa. These peptides or other substances might be important factors in intestinal development and maturation as well as in maintaining or enhancing intestinal function postnatally. We propose to accomplish two main goals: 1) enhance intestinal function by identifying certain agents that would not only alter intestinal morphology but improve intestinal absorption; and 2) establish a method of transplantation of fetal intestine that can be used to increase intestinal mucosal surface area. To accomplish these goals, we will use a model of transplanted fetal small intestine of the rat (previously utilized, see Appendix) placed in a subcutaneous location. The transplanted segment of small intestine is easily accessible and is thus ideal for: 1) obtaining mucosal biopsies for morphology, DNA synthesis and content, and disaccharidase determinations; and 2) perfusion techniques for absorption of substrates. In addition, fetal intestine can be evaluated as a means of increasing mucosal surface area by replacing the recipient's small intestine with the transplanted segment, and thereby maintaining adequate nutrition. By studying the alterations in intestinal function induced by manipulation of the local and systemic environment of the transplanted fetal intestine, which has a systemic blood supply and is denervated, we hope to provide information regarding the mechanisms responsible for intestinal maturation and adaptation. If enhancement of intestinal function can be accomplished by maximizing absorbing capacity or by adding mucosal surface area, infants with inadequate intestinal function may greatly benefit and perhaps survive.